Screening key biomarkers in papillary thyroid carcinoma: evidence from bioinformatic analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

AO Wei ,  YIN Detao

Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China;

Corresponding?author：

YIN Detao, Email: detaoyin@zzu.edu.cn

Keywords：

papillary thyroid carcinoma; differentially expressed gene; bioinformatic analysis

DOI：

10.7507/1007-9424.202006044

Video：

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Objective To understand the molecular mechanisms underlying the carcinogenesis and progression of papillary thyroid carcinoma (PTC), and provide candidate targets for diagnosis and treatment of PTC.Methods To identify the differentially expressed genes (DEGs) in the carcinogenesis and progression of PTC, the study was carried by analyzing the microarray datasets downloaded from gene expression omnibus (GEO) database, and making a series of studies including the protein-protein interaction network, KEGG and GO enrichment analyses of DEGs.Results A total of 339 DEGs and 10 hub genes were identified. While the expression of KIT was downregulated in the samples of PTC, the figures for FN1, CCND1, TIMP1, ICAM1, APOE, MET, RUNX2, KRT19 and SERPINA1 were upregulated. After the hypothesis test was corrected by multiple tests, the results showed that the changes of APOE [false discovery rate (FDR)=0.047 5] and KIT (FDR=0.042 0) gene expression had a certain impact on recurrence free survival (RFS) of PTC patients, which was statistically significant.Conclusions Survival analysis showed that FN1, ICAM1, APOE, MET, KRT19, KIT and SERPINA1 may be involved in the carcinogenesis or prognosis of PTC. However, further studies are needed to elucidate the biological function of these genes in PTC.

Citation： AO Wei, YIN Detao. Screening key biomarkers in papillary thyroid carcinoma: evidence from bioinformatic analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(3): 329-335. doi: 10.7507/1007-9424.202006044 Copy

1.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
2.	Wang X, Lu X, Geng Z, et al. LncRNA PTCSC3/miR-574-5p governs cell proliferation and migration of papillary thyroid carcinoma via Wnt/β-catenin signaling. J Cell Biochem, 2017, 118(12): 4745-4752.
3.	Chereau N, Giudicelli X, Pattou F, et al. Diffuse sclerosing variant of papillary thyroid carcinoma is associated with aggressive histopathological features and a poor outcome: results of a large multicentric study. J Clin Endocrinol Metab, 2016, 101(12): 4603-4610.
4.	Blomberg M, Feldt-Rasmussen U, Andersen KK, et al. Thyroid cancer in Denmark 1943-2008, before and after iodine supplementation. Int J Cancer, 2012, 131(10): 2360-2366.
5.	李偉, 潘燕, 李學軍. HER2 陽性乳腺癌治療藥物曲妥珠單抗耐藥機制及新一代靶向藥物研究進展. 中國臨床藥理學雜志, 2014, 30(1): 48-51.
6.	Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol, 2012, 196(4): 395-406.
7.	Wang L, Zhao L, Jia X, et al. Aminophenols increase proliferation of thyroid tumor cells by inducing the transcription factor activity of estrogen receptor α. Biomed Pharmacother, 2019, 109: 621-628.
8.	黑利娟, 王娟紅, 魏威, 等. 乳頭狀甲狀腺癌患者血清和甲狀腺組織中白細胞介素 6 水平的檢測及其意義. 吉林大學學報 (醫學版), 2019, 45(3): 601-605.
9.	Xiao M, Hu S, Tang J, et al. Interleukin(IL)-21 promoter polymorphism increases the risk of thyroid cancer in Chinese population. Gene, 2014, 537(1): 15-19.
10.	Santarpia L, El-Naggar AK, Cote GJ, et al. Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer. J Clin Endocrinol Metab, 2008, 93(1): 278-284.
11.	Levin-Salomon V, Livnah O, Engelberg D. A “molecular evolution” approach for isolation of intrinsically active (MEK-independent) MAP kinases. Methods Mol Biol, 2010, 661: 257-272.
12.	Hong H, Zhou T, Fang S, et al. Pigment epithelium-derived factor (PEDF) inhibits breast cancer metastasis by down-regulating fibronectin. Breast Cancer Res Treat, 2014, 148(1): 61-72.
13.	Kenny HA, Chiang CY, White EA, et al. Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion. J Clin Invest, 2014, 124(10): 4614-4628.
14.	Jeon M, Lee J, Nam SJ, et al. Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells. Exp Cell Res, 2015, 333(1): 116-126.
15.	周艷, 羅楓, 伍世鋼, 等. TPO、HBME-1、CK19、Galectin-3、CyclinD1 檢測在甲狀腺良惡性病變中的鑒別診斷價值. 海南醫學, 2020, 31(1): 27-30.
16.	傅曉丹, 樓善賢, 施紅旗, 等. 甲狀腺微小乳頭狀癌 254 例臨床病理分析. 中華病理學雜志, 2015, 44(4): 258-261.
17.	Zhang W, Sun W, Qin Y, et al. Knockdown of KDM1A suppresses tumour migration and invasion by epigenetically regulating the TIMP1/MMP9 pathway in papillary thyroid cancer. J Cell Mol Med, 2019, 23(8): 4933-4944.
18.	Buitrago D, Keutgen XM, Crowley M, et al. Intercellular adhesion molecule-1 (ICAM-1) is upregulated in aggressive papillary thyroid carcinoma. Ann Surg Oncol, 2012, 19(3): 973-980.
19.	崔演, 劉勝男, 張佰玲, 等. 甲狀腺乳頭狀癌組織中 ICAM-1 的表達及意義. 臨床與實驗病理學雜志, 2013, 29(6): 655-657.
20.	Ramirez R, Hsu D, Patel A, et al. Over-expression of hepatocyte growth factor/scatter (HGF/SF) and the HGF/SF receptor (cMET) are associated with a high risk of metastasis and recurrence for children and young adults with papillary thyroid carcinoma. Clin Endocrinol (Oxf), 2000, 53(5): 635-644.
21.	鄭炳行, 師天雄, 鄧建偉. C-MET 蛋白在甲狀腺癌合并頸部淋巴結轉移的研究. 中國醫藥科學, 2013, 3(9): 26-27, 43.
22.	龔婷, 王家東, 錢敏飛, 等. 相對定量 real time RT-PCR 檢測 Runx2 mRNA 在甲狀腺乳頭狀癌中的表達. 臨床耳鼻咽喉頭頸外科雜志, 2013, 27(4): 193-195.
23.	Han M, Chen L, Wang Y. miR-218 overexpression suppresses tumorigenesis of papillary thyroid cancer via inactivation of PTEN/PI3K/AKT pathway by targeting Runx2. Onco Targets Ther, 2018, 11: 6305-6316.
24.	Wang X, Xu X, Peng C, et al. BRAF^V600E-induced KRT19 expression in thyroid cancer promotes lymph node metastasis via EMT. Oncol Lett, 2019, 18(1): 927-935.
25.	An J, Yang J, Lee WH, et al. Diagnostic Kit of breast cancer via urine microbiome. Eur J Surg Oncol, 2020, 46(2): e33.
26.	Vierlinger K, Mansfeld MH, Koperek O, et al. Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation. BMC Med Genomics, 2011, 4: 30.
27.	An HJ, Koh HM, Song DH. Apolipoprotein E is a predictive marker for assessing non-small cell lung cancer patients with lymph node metastasis. Pathol Res Pract,, 2019, 215(10): 152607.
28.	Asare GA, Owusu-Boateng E, Asiedu B, et al. Oxidised low-density lipoprotein, a possible distinguishing lipid profile biomolecule between prostate cancer and benign prostatic hyperplasia. Andrologia, 2019, 51(8): e13321.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
2. Wang X, Lu X, Geng Z, et al. LncRNA PTCSC3/miR-574-5p governs cell proliferation and migration of papillary thyroid carcinoma via Wnt/β-catenin signaling. J Cell Biochem, 2017, 118(12): 4745-4752.
3. Chereau N, Giudicelli X, Pattou F, et al. Diffuse sclerosing variant of papillary thyroid carcinoma is associated with aggressive histopathological features and a poor outcome: results of a large multicentric study. J Clin Endocrinol Metab, 2016, 101(12): 4603-4610.
4. Blomberg M, Feldt-Rasmussen U, Andersen KK, et al. Thyroid cancer in Denmark 1943-2008, before and after iodine supplementation. Int J Cancer, 2012, 131(10): 2360-2366.
5. 李偉, 潘燕, 李學軍. HER2 陽性乳腺癌治療藥物曲妥珠單抗耐藥機制及新一代靶向藥物研究進展. 中國臨床藥理學雜志, 2014, 30(1): 48-51.
6. Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol, 2012, 196(4): 395-406.
7. Wang L, Zhao L, Jia X, et al. Aminophenols increase proliferation of thyroid tumor cells by inducing the transcription factor activity of estrogen receptor α. Biomed Pharmacother, 2019, 109: 621-628.
8. 黑利娟, 王娟紅, 魏威, 等. 乳頭狀甲狀腺癌患者血清和甲狀腺組織中白細胞介素 6 水平的檢測及其意義. 吉林大學學報 (醫學版), 2019, 45(3): 601-605.
9. Xiao M, Hu S, Tang J, et al. Interleukin(IL)-21 promoter polymorphism increases the risk of thyroid cancer in Chinese population. Gene, 2014, 537(1): 15-19.
10. Santarpia L, El-Naggar AK, Cote GJ, et al. Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer. J Clin Endocrinol Metab, 2008, 93(1): 278-284.
11. Levin-Salomon V, Livnah O, Engelberg D. A “molecular evolution” approach for isolation of intrinsically active (MEK-independent) MAP kinases. Methods Mol Biol, 2010, 661: 257-272.
12. Hong H, Zhou T, Fang S, et al. Pigment epithelium-derived factor (PEDF) inhibits breast cancer metastasis by down-regulating fibronectin. Breast Cancer Res Treat, 2014, 148(1): 61-72.
13. Kenny HA, Chiang CY, White EA, et al. Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion. J Clin Invest, 2014, 124(10): 4614-4628.
14. Jeon M, Lee J, Nam SJ, et al. Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells. Exp Cell Res, 2015, 333(1): 116-126.
15. 周艷, 羅楓, 伍世鋼, 等. TPO、HBME-1、CK19、Galectin-3、CyclinD1 檢測在甲狀腺良惡性病變中的鑒別診斷價值. 海南醫學, 2020, 31(1): 27-30.
16. 傅曉丹, 樓善賢, 施紅旗, 等. 甲狀腺微小乳頭狀癌 254 例臨床病理分析. 中華病理學雜志, 2015, 44(4): 258-261.
17. Zhang W, Sun W, Qin Y, et al. Knockdown of KDM1A suppresses tumour migration and invasion by epigenetically regulating the TIMP1/MMP9 pathway in papillary thyroid cancer. J Cell Mol Med, 2019, 23(8): 4933-4944.
18. Buitrago D, Keutgen XM, Crowley M, et al. Intercellular adhesion molecule-1 (ICAM-1) is upregulated in aggressive papillary thyroid carcinoma. Ann Surg Oncol, 2012, 19(3): 973-980.
19. 崔演, 劉勝男, 張佰玲, 等. 甲狀腺乳頭狀癌組織中 ICAM-1 的表達及意義. 臨床與實驗病理學雜志, 2013, 29(6): 655-657.
20. Ramirez R, Hsu D, Patel A, et al. Over-expression of hepatocyte growth factor/scatter (HGF/SF) and the HGF/SF receptor (cMET) are associated with a high risk of metastasis and recurrence for children and young adults with papillary thyroid carcinoma. Clin Endocrinol (Oxf), 2000, 53(5): 635-644.
21. 鄭炳行, 師天雄, 鄧建偉. C-MET 蛋白在甲狀腺癌合并頸部淋巴結轉移的研究. 中國醫藥科學, 2013, 3(9): 26-27, 43.
22. 龔婷, 王家東, 錢敏飛, 等. 相對定量 real time RT-PCR 檢測 Runx2 mRNA 在甲狀腺乳頭狀癌中的表達. 臨床耳鼻咽喉頭頸外科雜志, 2013, 27(4): 193-195.
23. Han M, Chen L, Wang Y. miR-218 overexpression suppresses tumorigenesis of papillary thyroid cancer via inactivation of PTEN/PI3K/AKT pathway by targeting Runx2. Onco Targets Ther, 2018, 11: 6305-6316.
24. Wang X, Xu X, Peng C, et al. BRAF^V600E-induced KRT19 expression in thyroid cancer promotes lymph node metastasis via EMT. Oncol Lett, 2019, 18(1): 927-935.
25. An J, Yang J, Lee WH, et al. Diagnostic Kit of breast cancer via urine microbiome. Eur J Surg Oncol, 2020, 46(2): e33.
26. Vierlinger K, Mansfeld MH, Koperek O, et al. Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation. BMC Med Genomics, 2011, 4: 30.
27. An HJ, Koh HM, Song DH. Apolipoprotein E is a predictive marker for assessing non-small cell lung cancer patients with lymph node metastasis. Pathol Res Pract,, 2019, 215(10): 152607.
28. Asare GA, Owusu-Boateng E, Asiedu B, et al. Oxidised low-density lipoprotein, a possible distinguishing lipid profile biomolecule between prostate cancer and benign prostatic hyperplasia. Andrologia, 2019, 51(8): e13321.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Screening key biomarkers in papillary thyroid carcinoma: evidence from bioinformatic analysis

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